Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Fry, Mark; Smith, Pauline; Hoyda, Ted D.; Duncan, Marnie; Ahima, Rexford S.; Sharkey, Keith A.; Ferguson, Alastair V.

doi:10.1523/jneurosci.2014-06.2006

Cited by 85 publications

(82 citation statements)

References 53 publications

(58 reference statements)

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“…All animal protocols conformed to the standards of the Canadian Council on Animal Care and the Queen's University Animal Care Committee. Cell cultures were prepared according to protocols modified from Fry et al (20) and Brewer (6). Briefly, three or four Sprague-Dawley (ϳ150 g) rats were decapitated, and the brains were quickly removed and placed into oxygenated, ice-cold artificial cerebral-spinal fluid containing the following (in mM): 124 NaCl, 2 KCl, 1.25 KH 2PO4, 2.0 CaCl2, 1.3 MgSO4, 20 NaHCO3, and 10 glucose.…”

Section: Methodsmentioning

confidence: 99%

“…Responsiveness of AP neurons to 1 M-1 pM ghrelin was determined by comparing membrane potential of neurons before and after direct application. AP neurons were considered responsive if their mean membrane potential demonstrated a shift of at least 4.5 mV or a change in firing frequency of greater than 1 Hz (over a 60-s period) during the 120 s after application compared with the 100 s before application (20). Outward K ϩ currents were elicited by step depolarizations from a holding potential of Ϫ100 mV.…”

Section: Methodsmentioning

confidence: 99%

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Ghrelin modulates electrical activity of area postrema neurons

Fry¹,

Ferguson²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Ghrelin, a peptide hormone secreted from the stomach, is known to have a potent appetite-stimulating activity. Recently, it has been shown that area postrema (AP), a caudal brain stem center that lacks a blood-brain barrier, is a key site of activity for ghrelin in stimulating appetite and regulating pancreatic protein secretion. In this study, we have examined the ability of ghrelin to regulate the electrical activity of area postrema neurons using patch-clamp electrophysiology. Using current-clamp configuration, we found that at a concentration of 10 nM, ghrelin caused inhibition in 19% of neurons tested, while a further 19% were excited by similar application of ghrelin. The remaining 62% of AP neurons were insensitive to ghrelin. These effects were concentration dependent, with an apparent EC 50 of 1.9 nM. Voltage-clamp recordings revealed that ghrelin caused a potentiation of voltage-gated K ϩ currents in neurons that exhibited a hyperpolarization and a potentiation of a depolarizing nonspecific cation current (NSCC) in those neurons that exhibited a depolarization of membrane potential. These are the first data showing that ghrelin exerts a direct effect on electrical activity of AP neurons and supports the notion that ghrelin can act via the AP to regulate energy homeostasis. patch clamp; action potential; sensory circumventricular organ; energy homeostasis GHRELIN IS AN ACYLATED 28-amino acid peptide hormone, which was discovered on the basis of its activity as an endogenous ligand for the growth hormone secretagogue receptor (GHSR) (35). Originally isolated from the stomach, ghrelin has also been shown to be expressed in various tissues, including the duodenum, adrenal gland, lung, and gonads (22), as well as in neurons in the hypothalamus (11). In addition to its role in the stimulation of growth hormone release in the pituitary, ghrelin is thought to play several roles in the regulation of energy balance. Circulating levels of ghrelin are increased in the fasting state and in anticipation of food (2, 12, 13). Conversely, ghrelin levels are attenuated by feeding and the presence of nutrients in the stomach (58), or by treatment with leptin (2). Administration of ghrelin potently stimulates food intake in rats (58, 64, 65), mice (2), and humans (63). These studies suggest a physiological role in initiation of feeding. Ghrelin is also suggested to play a role in long-term regulation of energy balance, as chronic administration of ghrelin causes weight gain by reducing fat utilization as an energy source (58). Lastly, ghrelin also plays a role in the digestion of food and the stimulation of gastric motility, acid secretion, and pancreatic protein secretion (38, 41).There is considerable interest as to the mechanism by which ghrelin exerts its appetite-stimulating effects, and, in particular, the site of action of ghrelin in the central nervous system (CNS). For example, the neuropeptide Y/Agouti-related peptide (NPY/AGRP) neurons within the arcuate nucleus of the hypothalamus (ARC) are suggested by many t...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Ghrelin modulates electrical activity of area postrema neurons

Fry¹,

Ferguson²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Although previous studies have indicated the presence of AdipoR1 and AdipoR2 in the brain (16,20,21), the distribution of these receptors in discrete brain areas implicated in mood regulation remain unclear. In situ hybridization with specific cRNA probes revealed that AdipoR1 mRNA was highly expressed in various brain regions, such as the medial prefrontal cortex (mPFC), hippocampus, and amygdala (Fig.…”

Section: Adiponectin Haploinsufficiency Impairs Glucocorticoid-mediatedmentioning

confidence: 97%

“…injection (16). Previous studies have demonstrated the presence of adiponectin receptors, AdipoR1 and AdipoR2, in the central nervous system (16,(18)(19)(20)(21); however, their expression patterns in discrete brain areas remain to be determined.…”

mentioning

confidence: 99%

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Liu¹,

Guo²,

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

152

162

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Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressantlike behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.

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“…Cells in the AP were either hyperpolarized or depolarized by adiponectin, thus proving a possible mechanism for the central regulation of cardiovascular function (98).…”

Section: Note Added In Proofmentioning

confidence: 99%

Brain Adipocytokine Action and Metabolic Regulation

et al. 2006

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Adipose tissue secretes factors that control various physiological systems. The fall in leptin during fasting mediates hyperphagia and suppresses thermogenesis, thyroid and reproductive hormones, and immune system. On the other hand, rising leptin levels in the fed state stimulate fatty acid oxidation, decrease appetite, and limit weight gain. These divergent effects of leptin occur through neuronal circuits in the hypothalamus and other brain areas. Leptin also regulates the activities of enzymes involved in lipid metabolism, e.g., AMP-activated protein kinase and stearoyl-CoA desaturase-1, and also interacts with insulin signaling in the brain. Adiponectin enhances fatty acid oxidation and insulin sensitivity, in part by stimulating AMP-activated protein kinase phosphorylation and activity in liver and muscle. Moreover, adiponectin decreases body fat by increasing energy expenditure and lipid catabolism. These effects involve peripheral and possibly central mechanisms. Adipose tissue mediates interconversion of steroid hormones and secretes proinflammatory cytokines, vasoactive peptides, and coagulation and complement proteins. Understanding the actions of these "adipocytokines" will provide insight into the pathogenesis and treatment of obesity and related diseases. Diabetes 55 (Suppl. 2): S145-S154, 2006 ADIPOSE TISSUE

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Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Cited by 85 publications

References 53 publications

Ghrelin modulates electrical activity of area postrema neurons

Ghrelin modulates electrical activity of area postrema neurons

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Brain Adipocytokine Action and Metabolic Regulation

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